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Drug overview for CARDENE I.V. (nicardipine hcl):
Generic name: NICARDIPINE HCL
Drug class: Calcium Channel Blockers
Therapeutic class: Cardiovascular Therapy Agents
Nicardipine hydrochloride is a 1,4-dihydropyridine-derivative calcium-channel blocking agent (calcium-channel blocker).
No enhanced Uses information available for this drug.
Generic name: NICARDIPINE HCL
Drug class: Calcium Channel Blockers
Therapeutic class: Cardiovascular Therapy Agents
Nicardipine hydrochloride is a 1,4-dihydropyridine-derivative calcium-channel blocking agent (calcium-channel blocker).
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for CARDENE I.V. (nicardipine hcl) have been approved by the FDA:
Indications:
Hypertension
Professional Synonyms:
Elevated blood pressure
Essential hypertension
Hyperpiesia
Hyperpiesis
Hypertensive disorder
Systemic arterial hypertension
Indications:
Hypertension
Professional Synonyms:
Elevated blood pressure
Essential hypertension
Hyperpiesia
Hyperpiesis
Hypertensive disorder
Systemic arterial hypertension
The following dosing information is available for CARDENE I.V. (nicardipine hcl):
Dosage adjustment of nicardipine hydrochloride generally does not appear to be necessary for geriatric patients unless renal and/or hepatic impairment is present.
As monotherapy for the management of hypertension, the usual initial adult oral dosage of nicardipine hydrochloride extended-release capsules is 30 mg twice daily and the usual maintenance dosage is 30-60 mg twice daily. The manufacturer states that the effective antihypertensive dosage range in clinical studies in adults was 30-60 mg twice daily as extended-release capsules.
Dosage of nicardipine hydrochloride extended-release capsules should be adjusted according to the patient's blood pressure response 2-4 hours after oral dosing as well as just prior to the next dose. Maximal blood pressure response generally is sustained from 2-6 hours after an oral dose at steady state. The possibility of symptomatic hypotension should be considered during nicardipine hydrochloride dosing, particularly when initiating therapy with the drug or with upward dosage titration.
Avoidance of hypotension is especially important in patients who have sustained an acute cerebral infarction or hemorrhage.
When switching from conventional to extended-release nicardipine hydrochloride capsules, the total daily dose as conventional capsules may not be a useful guide in judging the effective antihypertensive dose as extended-release capsules. However, therapy with extended-release capsules can be initiated with the currently effective total daily dosage of conventional capsules, but administered in 2 rather than 3 divided doses, and then dosage subsequently should be adjusted according to blood pressure response and patient tolerance.
Experts generally recommend the use of extended-release nicardipine for the management of hypertension because of less frequent dosing, potentially smoother blood pressure control, and concerns raised by experience with short-acting (conventional, immediate-release) nifedipine. If nicardipine hydrochloride as conventional capsules is used, the usual initial adult oral dosage is 20 mg 3 times daily. The manufacturers state that the effective antihypertensive dosage range in clinical studies in adults was 20-40 mg 3 times daily as conventional capsules.
Dosage of the drug should be adjusted according to the patient's peak (approximately 1-2 hours after dosing) and trough (8 hours after dosing) blood pressure responses, but generally no more frequently than at 3-day intervals. The possibility of substantial differences between peak and trough blood pressure responses to nicardipine should be considered. Because of nicardipine's prominent peak antihypertensive effect and the risk of symptomatic hypotension, assessment of blood pressure response 1-2 hours after dosing is particularly important during initial titration.
Avoidance of hypotension is especially important in patients who have sustained an acute cerebral infarction or hemorrhage.
For the short-term management of hypertension when oral therapy is not feasible or desirable, nicardipine hydrochloride may be administered as a slow, continuous IV infusion. For patients who were maintained on oral nicardipine therapy and are being switched temporarily to IV therapy, the manufacturer of parenteral nicardipine hydrochloride states that the infusion rates necessary to produce an average plasma concentration equivalent to steady-state oral dosages are as follow: 0.5 mg/hour for a conventional capsule dosage of 20 mg every 8 hours, 1.2
mg/hour for a conventional capsule dosage of 30 mg every 8 hours, and 2.2 mg/hour for a conventional capsule dosage of 40 mg every 8 hours.
For gradual reduction in acute hypertensive episodes in patients with chronic hypertension who were not receiving oral nicardipine hydrochloride therapy, the IV infusion may be initiated at a rate of 5 mg/hour. If the desired blood pressure reduction is not achieved at this dosage, the infusion rate may be increased by 2.5 mg/hour every 15 minutes up to a maximum of 15 mg/hour, until the desired blood pressure reduction is achieved.
For more rapid blood pressure reduction, the infusion may be initiated at a rate of 5 mg/hour and, if the desired blood pressure reduction is not achieved at this dosage, the infusion rate may be increased by 2.5 mg/hour every 5 minutes up to a maximum of 15 mg/hour, until the desired blood pressure reduction is achieved. Following achievement of the desired blood pressure, the infusion rate should be decreased to 3 mg/hour.
The rate of infusion should be adjusted as necessary to maintain the desired blood pressure response. If there is concern about impending hypotension or tachycardia during the infusion, the infusion should be discontinued; once blood pressure has stabilized, the infusion may be restarted at low dosages (e.g., 3-5 mg/hour) and adjusted to maintain the desired blood pressure response. Avoidance of hypotension is especially important in patients who have sustained an acute cerebral infarction or hemorrhage.
When nicardipine hydrochloride is used in the management of a hypertensive emergency in adults, the usual dosage of the drug as an IV infusion is 5-15 mg/hour, adjusted according to blood pressure response and tolerance. Patients who have hypertensive crisis with a compelling indication (e.g., aortic dissection, severe preeclampsia, eclampsia, pheochromocytoma crisis) should have their systolic blood pressure reduced to less than 140 mm Hg during the first hour and, in patients with acute aortic dissection, to less than 120 mm Hg within the first 20 minutes. The initial goal of such therapy in adults without a compelling indication is to reduce systolic blood pressure by no more than 25% within the first hour, followed by further blood pressure reduction if stable to 160/110 to 160/100 mm Hg within the next 2-6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.
If this blood pressure is well tolerated and the patient is clinically stable, further gradual reductions toward normal can be implemented in the next 24-48 hours.
For rapid reduction of blood pressure in children and adolescents+ with severe hypertension and life-threatening symptoms, some experts recommend administration of nicardipine hydrochloride as a rapid IV (''bolus'') dose of 30 mcg/kg (up to 2 mg) or an IV infusion of 0.5-4 mcg/kg per minute. These experts suggest that blood pressure should be reduced by no more than 25% of the planned reduction over the first 8 hours.
For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
For prolonged control of blood pressure, patients should be transferred to oral therapy as soon as their clinical condition permits. When transferring to an oral antihypertensive agent other than nicardipine, therapy generally should be initiated upon discontinuance of IV nicardipine. If nicardipine hydrochloride conventional capsules are to be used, the first dose of a 3-times daily regimen should be administered 1 hour prior to discontinuance of the IV infusion.
The elimination of nicardipine, including on first pass through the liver, may be impaired substantially in patients with hepatic impairment or reduced hepatic blood flow regardless of whether the drug is administered orally or parenterally. Therefore, the drug should be used with caution and the dosing frequency of conventional capsules reduced from 3 times daily to twice daily for initiation and maintenance of nicardipine hydrochloride therapy in such patients. Reduced dosages also should be considered for such patients receiving nicardipine IV.
In patients with severe liver disease, oral bioavailability may be increased up to fourfold and elimination half-life prolonged substantially (e.g., to 19 hours). The use of nicardipine hydrochloride extended-release capsules has not been studied in patients with severe hepatic impairment. Because high doses of IV nicardipine hydrochloride (e.g., 5 mg over 20 minutes) have been reported to increase the hepatic venous gradient pressure by 4 mm Hg in cirrhotic patients, the drug should be used IV with caution in patients with portal hypertension; therefore, careful IV dosage titration also is recommended for patients with impaired renal function.
For the management of hypertension or chronic stable angina in patients with severely impaired hepatic function, nicardipine hydrochloride should be initiated at an oral dosage of 20 mg twice daily as conventional capsules. Subsequent dosage should be individualized based on clinical findings, but the manufacturer recommends that a twice-daily dosing schedule be maintained.
Careful titration of nicardipine hydrochloride dosage also is recommended for patients with renal impairment. The manufacturer states that plasma concentrations achieved and oral bioavailability may be increased approximately twofold with conventional capsules in patients with mild impairment (serum creatinine concentration of 1.2-5.5 mg/dL) compared with healthy individuals and twofold to threefold with extended-release capsules in patients with moderate impairment (creatinine clearance of 10-55 mL/minute) compared with those with mild impairment (creatinine clearance exceeding 55 mL/minute). With extended-release capsules, plasma concentrations and oral bioavailability of the drug appear to be similar in patients with mild impairment compared with healthy individuals.
In patients with moderate renal impairment receiving IV nicardipine, systemic clearance was substantially lower and area under the plasma concentration-time curve (AUC) was substantially higher.
For the management of hypertension or chronic stable angina in patients with renal impairment, nicardipine hydrochloride therapy should be initiated orally at a dosage of 20 mg 3 times daily as conventional capsules or 30 mg twice daily as extended-release capsules. Subsequent dosage should be titrated carefully based on blood pressure response and patient tolerance.
As monotherapy for the management of hypertension, the usual initial adult oral dosage of nicardipine hydrochloride extended-release capsules is 30 mg twice daily and the usual maintenance dosage is 30-60 mg twice daily. The manufacturer states that the effective antihypertensive dosage range in clinical studies in adults was 30-60 mg twice daily as extended-release capsules.
Dosage of nicardipine hydrochloride extended-release capsules should be adjusted according to the patient's blood pressure response 2-4 hours after oral dosing as well as just prior to the next dose. Maximal blood pressure response generally is sustained from 2-6 hours after an oral dose at steady state. The possibility of symptomatic hypotension should be considered during nicardipine hydrochloride dosing, particularly when initiating therapy with the drug or with upward dosage titration.
Avoidance of hypotension is especially important in patients who have sustained an acute cerebral infarction or hemorrhage.
When switching from conventional to extended-release nicardipine hydrochloride capsules, the total daily dose as conventional capsules may not be a useful guide in judging the effective antihypertensive dose as extended-release capsules. However, therapy with extended-release capsules can be initiated with the currently effective total daily dosage of conventional capsules, but administered in 2 rather than 3 divided doses, and then dosage subsequently should be adjusted according to blood pressure response and patient tolerance.
Experts generally recommend the use of extended-release nicardipine for the management of hypertension because of less frequent dosing, potentially smoother blood pressure control, and concerns raised by experience with short-acting (conventional, immediate-release) nifedipine. If nicardipine hydrochloride as conventional capsules is used, the usual initial adult oral dosage is 20 mg 3 times daily. The manufacturers state that the effective antihypertensive dosage range in clinical studies in adults was 20-40 mg 3 times daily as conventional capsules.
Dosage of the drug should be adjusted according to the patient's peak (approximately 1-2 hours after dosing) and trough (8 hours after dosing) blood pressure responses, but generally no more frequently than at 3-day intervals. The possibility of substantial differences between peak and trough blood pressure responses to nicardipine should be considered. Because of nicardipine's prominent peak antihypertensive effect and the risk of symptomatic hypotension, assessment of blood pressure response 1-2 hours after dosing is particularly important during initial titration.
Avoidance of hypotension is especially important in patients who have sustained an acute cerebral infarction or hemorrhage.
For the short-term management of hypertension when oral therapy is not feasible or desirable, nicardipine hydrochloride may be administered as a slow, continuous IV infusion. For patients who were maintained on oral nicardipine therapy and are being switched temporarily to IV therapy, the manufacturer of parenteral nicardipine hydrochloride states that the infusion rates necessary to produce an average plasma concentration equivalent to steady-state oral dosages are as follow: 0.5 mg/hour for a conventional capsule dosage of 20 mg every 8 hours, 1.2
mg/hour for a conventional capsule dosage of 30 mg every 8 hours, and 2.2 mg/hour for a conventional capsule dosage of 40 mg every 8 hours.
For gradual reduction in acute hypertensive episodes in patients with chronic hypertension who were not receiving oral nicardipine hydrochloride therapy, the IV infusion may be initiated at a rate of 5 mg/hour. If the desired blood pressure reduction is not achieved at this dosage, the infusion rate may be increased by 2.5 mg/hour every 15 minutes up to a maximum of 15 mg/hour, until the desired blood pressure reduction is achieved.
For more rapid blood pressure reduction, the infusion may be initiated at a rate of 5 mg/hour and, if the desired blood pressure reduction is not achieved at this dosage, the infusion rate may be increased by 2.5 mg/hour every 5 minutes up to a maximum of 15 mg/hour, until the desired blood pressure reduction is achieved. Following achievement of the desired blood pressure, the infusion rate should be decreased to 3 mg/hour.
The rate of infusion should be adjusted as necessary to maintain the desired blood pressure response. If there is concern about impending hypotension or tachycardia during the infusion, the infusion should be discontinued; once blood pressure has stabilized, the infusion may be restarted at low dosages (e.g., 3-5 mg/hour) and adjusted to maintain the desired blood pressure response. Avoidance of hypotension is especially important in patients who have sustained an acute cerebral infarction or hemorrhage.
When nicardipine hydrochloride is used in the management of a hypertensive emergency in adults, the usual dosage of the drug as an IV infusion is 5-15 mg/hour, adjusted according to blood pressure response and tolerance. Patients who have hypertensive crisis with a compelling indication (e.g., aortic dissection, severe preeclampsia, eclampsia, pheochromocytoma crisis) should have their systolic blood pressure reduced to less than 140 mm Hg during the first hour and, in patients with acute aortic dissection, to less than 120 mm Hg within the first 20 minutes. The initial goal of such therapy in adults without a compelling indication is to reduce systolic blood pressure by no more than 25% within the first hour, followed by further blood pressure reduction if stable to 160/110 to 160/100 mm Hg within the next 2-6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.
If this blood pressure is well tolerated and the patient is clinically stable, further gradual reductions toward normal can be implemented in the next 24-48 hours.
For rapid reduction of blood pressure in children and adolescents+ with severe hypertension and life-threatening symptoms, some experts recommend administration of nicardipine hydrochloride as a rapid IV (''bolus'') dose of 30 mcg/kg (up to 2 mg) or an IV infusion of 0.5-4 mcg/kg per minute. These experts suggest that blood pressure should be reduced by no more than 25% of the planned reduction over the first 8 hours.
For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
For prolonged control of blood pressure, patients should be transferred to oral therapy as soon as their clinical condition permits. When transferring to an oral antihypertensive agent other than nicardipine, therapy generally should be initiated upon discontinuance of IV nicardipine. If nicardipine hydrochloride conventional capsules are to be used, the first dose of a 3-times daily regimen should be administered 1 hour prior to discontinuance of the IV infusion.
The elimination of nicardipine, including on first pass through the liver, may be impaired substantially in patients with hepatic impairment or reduced hepatic blood flow regardless of whether the drug is administered orally or parenterally. Therefore, the drug should be used with caution and the dosing frequency of conventional capsules reduced from 3 times daily to twice daily for initiation and maintenance of nicardipine hydrochloride therapy in such patients. Reduced dosages also should be considered for such patients receiving nicardipine IV.
In patients with severe liver disease, oral bioavailability may be increased up to fourfold and elimination half-life prolonged substantially (e.g., to 19 hours). The use of nicardipine hydrochloride extended-release capsules has not been studied in patients with severe hepatic impairment. Because high doses of IV nicardipine hydrochloride (e.g., 5 mg over 20 minutes) have been reported to increase the hepatic venous gradient pressure by 4 mm Hg in cirrhotic patients, the drug should be used IV with caution in patients with portal hypertension; therefore, careful IV dosage titration also is recommended for patients with impaired renal function.
For the management of hypertension or chronic stable angina in patients with severely impaired hepatic function, nicardipine hydrochloride should be initiated at an oral dosage of 20 mg twice daily as conventional capsules. Subsequent dosage should be individualized based on clinical findings, but the manufacturer recommends that a twice-daily dosing schedule be maintained.
Careful titration of nicardipine hydrochloride dosage also is recommended for patients with renal impairment. The manufacturer states that plasma concentrations achieved and oral bioavailability may be increased approximately twofold with conventional capsules in patients with mild impairment (serum creatinine concentration of 1.2-5.5 mg/dL) compared with healthy individuals and twofold to threefold with extended-release capsules in patients with moderate impairment (creatinine clearance of 10-55 mL/minute) compared with those with mild impairment (creatinine clearance exceeding 55 mL/minute). With extended-release capsules, plasma concentrations and oral bioavailability of the drug appear to be similar in patients with mild impairment compared with healthy individuals.
In patients with moderate renal impairment receiving IV nicardipine, systemic clearance was substantially lower and area under the plasma concentration-time curve (AUC) was substantially higher.
For the management of hypertension or chronic stable angina in patients with renal impairment, nicardipine hydrochloride therapy should be initiated orally at a dosage of 20 mg 3 times daily as conventional capsules or 30 mg twice daily as extended-release capsules. Subsequent dosage should be titrated carefully based on blood pressure response and patient tolerance.
Nicardipine hydrochloride usually is administered orally, but may be administered by slow, continuous IV infusion when oral administration is not feasible or desired. For prolonged therapy, patients should be transferred to oral therapy as soon as their clinical condition permits. Some experts state that nicardipine hydrochloride may also be administered as a direct IV (''bolus'') injection+ in children and adolescents with acute severe hypertension and life-threatening symptoms.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for CARDENE I.V. (nicardipine hcl):
There are 0 contraindications.
There are 3 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Selected Macrolides/Selected Calcium Channel Blockers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Some macrolides may inhibit metabolism of calcium channel blockers.(1) In some patients, calcium channel blockers may inhibit the metabolism of the macrolide. Some macrolides have been associated with cardiac arrhythmias, including torsades de pointes.(2) CLINICAL EFFECTS: In some patients, concurrent use may result in elevated levels of and effects from the calcium channel blockers, including hypotension,(2,3) shock,(2) and acute kidney failure.(3) In others, elevated levels of the macrolide may occur, which may increase the risk of sudden death from cardiac causes.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid the concurrent use of calcium channel blockers with macrolides that inhibit CYP.(1,2) Depending on the infection, azithromycin may be an alternative in patients maintained on calcium channel blockers.(1) If concurrent use is required, monitor patients for and instruct them to report signs of hypotension, cardiac arrhythmias, or renal failure. DISCUSSION: A retrospective review examined sudden cardiac death in Tennessee Medicaid patients. Erythromycin use increased the risk of sudden cardiac death by 1.79-fold. Concurrent use of erythromycin with a potent inhibitor of CYP3A4 (diltiazem, fluconazole, itraconazole, ketoconazole, troleandomycin, or verapamil) increased the risk of sudden cardiac death by 5.35-fold when compared to patients receiving no antibiotic therapy.(2) In a retrospective review of residents of Ontario, Canada aged 66 or older who were receiving calcium channel blockers, use of clarithromycin and erythromycin were associated with an increased risk of hospitalization for hypotension (odds ratio 3.7 and 5.8, respectively). There was no association between use of azithromycin and hospitalization for hypotension.(2) In a retrospective review of residents of Ontario, Canada aged 65 or older who were receiving calcium channel blockers, use of clarithromycin was associated with an increased risk of hospitalization with acute kidney injury when compared to use of azithromycin (0.44% of patients versus 0.22% - odds ratio 1.98). Risk was highest with the use of nifedipine (odds ratio 5.33). Use of clarithromycin was also associated with a higher risk of hospitalization with hypotension (0.12% of patients versus 0.07%, odds ratio 1.60) and all-cause mortality (1.02% of patients versus 0.59%, odds ratio 1.74).(3) In a cross-over study in 12 healthy male subjects, the administration of a single dose of felodipine (10 mg extended-release) after four doses of erythromycin (250 mg) resulted in an increase in felodipine area-under-curve (AUC), maximum concentration (Cmax), and half-life by 149%, 127%, and 61%, respectively. Concurrent administration increased dehydrofelodipine AUC, Cmax, and half-life by 92%, 56%, and 93%, respectively, when compared to felodipine administration alone. Concurrent administration of felodipine and erythromycin decreased felodipine M3 metabolite AUC and Cmax concentrations by 41% and 36%, respectively. The extent of the interaction was extremely variable between subjects.(4) In a case report, a 43 year-old female developed palpitations, flushing, ankle edema, and hypotension 2-4 days after the addition of erythromycin to felodipine therapy. Felodipine levels were found to be elevated.(5) In a case report, a 77 year-old male developed shock, heart block, and multi-organ failure two days after the addition of clarithromycin to nifedipine therapy.(6) In a case report, a 76 year-old female developed hypotension, bradycardia, shortness of breath, and weakness two days after the addition of telithromycin to verapamil therapy.(7) |
CLARITHROMYCIN, CLARITHROMYCIN ER, E.E.S. 200, E.E.S. 400, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, LANSOPRAZOL-AMOXICIL-CLARITHRO, OMECLAMOX-PAK, VOQUEZNA TRIPLE PAK |
| Dantrolene/Calcium Channel Blockers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Dantrolene may decrease the release of calcium from the sarcoplasmic reticulum, resulting in additive or synergistic effects with calcium channel blockers.(1) CLINICAL EFFECTS: Concurrent use of dantrolene and calcium channel blockers may result in cardiogenic shock.(2-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US, UK, and Australian manufacturers of dantrolene state that concurrent use with calcium channel blockers during the management of malignant hyperthermia crisis is not recommended.(2-4) The Australian and UK manufacturers of diltiazem state that concurrent use of dantrolene infusion with calcium channel blockers is contraindicated.(5-6) DISCUSSION: Cardiogenic shock in patients treated simultaneously with verapamil and dantrolene is rare but has been reported.(2-4,7) Concurrent use of dantrolene and verapamil in swine has been reported to result in cardiogenic shock and hyperkalemia.(8) In dogs, the combination has been reported to cause hyperkalemia.(9) The combination of diltiazem and dantrolene has been reported to cause adverse cardiovascular effects in swine.(10) A study in swine showed no adverse effects from the combination of dantrolene and nifedipine(10) and one patient who experience cardiogenic shock with dantrolene and verapamil had no adverse effects with the combination of dantrolene and nifedipine;(7) however, the US manufacturer cannot endorse the safety of the combination.(2) |
DANTRIUM, DANTROLENE SODIUM, REVONTO, RYANODEX |
| Tacrolimus/Nicardipine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Nicardipine may inhibit the metabolism of tacrolimus by CYP3A4.(1-7) CLINICAL EFFECTS: Concurrent use of nicardipine may result in elevated levels of and side effects from tacrolimus, including nephrotoxicity, prolongation of the QTc interval and life-threatening cardiac arrhythmias, torsades de pointes, graft dysfunction, and increased risk of infections.(1-7) PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age. Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction). PATIENT MANAGEMENT: Patients maintained on tacrolimus should be closely monitored if nicardipine is initiated or discontinued. The dosage of tacrolimus may need to be adjusted or nicardipine may need to be discontinued. Consider an alternative antihypertensive agent, such as labetalol. When concurrent therapy of nicardipine and tacrolimus is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a clinical study, eight patients who were CYP3A5 non-expressors had a higher median concentration maximum (Cmax) than both four patients CYP3A5 expressors and controls (24.3 ng/ml, 13.9 ng/mL, and 14.6 ng/ml, respectively). Compared to the other two groups, CYP3A5 non-expressors had higher dose adjusted Cmax, less time to Cmax, and more scheduled tacrolimus doses held per patient. Six of eight CYP3A5 non-expressors had potentially toxic Cmax levels (> 20 ng/ml) compared with none of four CYP3A5 expressors and 11.25% of control group.(5) A case report of a 20-year-old kidney transplant patient on tacrolimus 5 mg twice daily, mycophenolate mofetil, and prednisone was started on intravenous nicardipine. Twelve hours after starting nicardipine, the tacrolimus trough level was 16.3 ng/mL (target range 12-18 ng/mL). Tacrolimus dose was reduced.(6) |
ASTAGRAF XL, ENVARSUS XR, PROGRAF, TACROLIMUS, TACROLIMUS XL |
There are 11 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Digoxin/Selected Calcium Channel Blockers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Calcium channel blockers may inhibit the renal clearance of digoxin through an unknown mechanism. CLINICAL EFFECTS: Plasma digoxin concentrations may be elevated. In addition, the negative chronotropic effects of digoxin and bepridil are additive, resulting in a cumulative decrease in heart rate. Symptoms of digoxin toxicity can include anorexia, nausea, vomiting, headache, fatigue, malaise, drowsiness, generalized muscle weakness, disorientation, hallucinations, visual disturbances, and arrhythmias. PREDISPOSING FACTORS: Low body weight, advanced age, impaired renal function, hypokalemia, hypercalcemia, and/or hypomagnesemia may increase the risk of digoxin toxicity. PATIENT MANAGEMENT: If concurrent therapy is warranted, monitor serum digoxin levels and observe the patient for symptoms of digoxin toxicity. Upon adding a calcium channel blocker, digoxin should first be decreased in anticipation of interaction, then adjust the dosage accordingly. The dosage of digoxin may need to be decreased by 15-50% or the frequency of administration may be reduced. DISCUSSION: The effect of bepridil on steady-state serum digoxin levels was studied in a randomized, double-blind investigation. Concurrent administration of bepridil and digoxin produced a 34% increase in serum digoxin levels compared to administration of digoxin alone. Concomitant administration of both drugs was associated with additive negative chronotropic effects. Information on the effects of diltiazem on digoxin concentrations are conflicting. Several studies have reported that concurrent use of digoxin and diltiazem led to an increased steady state digoxin level as well as an increased digoxin area-under-curve (AUC) and decreased renal clearance, and reduced volume of distribution. However, one of these studies reported no significant change in digoxin half-life, peak concentration (Cmax), time to Cmax (Tmax), or volume of distribution, and seven other studies reported no effect of diltiazem on serum digoxin concentrations or renal digoxin clearance. Concomitant isradipine administration significantly decreased (by 9%) the the digoxin volume of distribution and increased (by 25%) digoxin Cmax; however, the digoxin steady state serum concentration, AUC, and renal clearance were not affected. In patients with congestive heart failure on digoxin therapy, the addition of felodipine resulted in a significant increase in digoxin Cmax attained following oral administration. This increase was most notable in patients with high felodipine serum concentrations. Digoxin trough levels and six hour post-dose levels were unaffected; as were digoxin AUC measurements. There is one case report of an interaction between nifedipine and digoxin; however, a study in 28 patients found no effect of nifedipine on digoxin. A study in ten subjects showed that nisoldipine increased digoxin levels by 15%. Information on the effects of nicardipine on digoxin kinetics is conflicting. One study in twenty patients showed no effect of nicardipine on digoxin. One study in ten subjects showed a significant increase in digoxin levels: however, this was seen in only one subject. Concurrent nitrendipine has been shown to increase digoxin serum levels by 57% and digoxin AUC by 15%. Concurrent diltiazem has been shown to increase digoxin serum concentration by 20%. Concurrent nifedipine has been shown to increase digoxin serum concentration by 45%. |
DIGITEK, DIGOXIN, DIGOXIN MICRONIZED, LANOXIN, LANOXIN PEDIATRIC |
| Cyclosporine/Calcium Channel Blockers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Calcium channel blockers may inhibit the metabolism of cyclosporine by CYP3A4. CLINICAL EFFECTS: Concurrent use of calcium channel blockers may result in elevated levels of and toxicity from cyclosporine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor cyclosporine levels when initiating or discontinuing calcium channel blockers. DISCUSSION: Concurrent administration of cyclosporine and amlodipine, diltiazem, nicardipine, or verapamil has caused elevated cyclosporine levels. Renal toxicity was seen in some cases. Upon discontinuation of the calcium channel blocker, cyclosporine concentrations have returned to baseline levels. With concurrent diltiazem administration, cyclosporine dosage decreases of 15% to 48% were required. A prospective study in 11 renal transplant patients showed a 40% increase in trough cyclosporine levels when given concomitantly with amlodipine.(29) |
CYCLOSPORINE, CYCLOSPORINE MODIFIED, GENGRAF, NEORAL, SANDIMMUNE |
| Selected Calcium Channel Blockers/Cimetidine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Cimetidine may decrease the metabolism of diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, and nitrendipine. CLINICAL EFFECTS: The pharmacological effects of the calcium channel blocker may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Observe the patient for changes in clinical response to the calcium channel blocker when starting or stopping cimetidine. The dosage of the calcium channel blocker may need to be adjusted. Ideally, suggest an alternative H-2 antagonist such as famotidine, nizatidine, or ranitidine. DISCUSSION: Significant effects have been observed during concurrent administration of nifedipine or felodipine with cimetidine. During combined administration of nifedipine and cimetidine in six healthy volunteers, the area-under-curve (AUC) of nifedipine was increased by 80% compared to nifedipine alone. Increased heart rate and a drop in mean arterial pressure 14 mmHg were also reported. Ranitidine showed only a nonsignificant 25% rise in peak plasma levels of nifedipine and no effects on blood pressure. Similar results were reported in another study where concurrent administration of felodipine and cimetidine resulted in an increase in felodipine AUC and maximum concentration (Cmax) by 50%. Concurrent administration of cimetidine has also been shown to increase the AUC and Cmax of diltiazem by 53% and 58%, respectively. The manufacturers of isradipine and nicardipine recommend carefully monitoring patients receiving concurrent therapy with cimetidine. The manufacturer of isradipine states that concurrent therapy with cimetidine has been shown to increase the AUC of isradipine by 50%. The manufacturer of nifedipine states that careful titration is necessary in patients receiving concurrent therapy. The manufacturers of felodipine and diltiazem state that dosage adjustments may be necessary in patients receiving concurrent therapy. Ranitidine has much less affinity for CYP metabolism than cimetidine and would therefore be expected to have less of an effect on calcium channel blocker metabolism. Studies have shown that nizatidine and famotidine do not inhibit CYP3A4 metabolism. |
CIMETIDINE |
| Slt Calcium Channel Blockers/Atazanavir;Darunavir;Fosamprenavir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Atazanavir, darunavir, and fosamprenavir may inhibit the CYP3A4-mediated metabolism of calcium channel blockers.(1-5) CLINICAL EFFECTS: Concurrent use of atazanavir, darunavir, or fosamprenavir may result in increased levels of calcium channel blockers. The combination of atazanavir with non-dihydropyridines may result in an additive effect on the PR interval.(1-2,6-7) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US Department of Health and Human Services HIV guidelines recommend that concurrent use of calcium channel blockers with protease inhibitors be monitored closely. The dose of the calcium channel blocker should be titrated to clinical response and adverse events.(5) Additional recommendations apply to patients on atazanavir. EKG monitoring is recommended for patients on concurrent therapy with calcium channel blockers. A dose reduction of diltiazem by 50% should be considered for patients starting atazanavir.(1,2,5) DISCUSSION: In a study in 28 subjects, concurrent atazanavir (400 mg daily) with diltiazem (180 mg daily) increased the diltiazem area-under-curve (AUC) and maximum concentration (Cmax) by 225% and 98%, respectively.(1,2) Diltiazem minimum concentration (Cmin) increased by 242%. The Cmax, AUC, and Cmin of desacetyl-diltiazem increased by 272%, 265%, and 221%, respectively. There were no significant effects on atazanavir levels.(1) |
ATAZANAVIR SULFATE, DARUNAVIR, EVOTAZ, FOSAMPRENAVIR CALCIUM, PREZCOBIX, PREZISTA, REYATAZ, SYMTUZA |
| Sirolimus;Temsirolimus/Selected Calcium Channel Blockers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Some calcium channel blockers may inhibit the metabolism of sirolimus and temsirolimus by CYP3A4.(1-3) CLINICAL EFFECTS: Concurrent use of calcium channel blockers may result in elevated levels of and side effects from sirolimus and temsirolimus.(1-3) Concurrent sirolimus and verapamil may result in elevated levels of and effects from verapamil.(1) Sirolimus is the active metabolite of temsirolimus,(3) therefore, temsirolimus should be expected to act in the same manner as sirolimus. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients maintained on sirolimus should be closely monitored if calcium channel blockers such as diltiazem, nicardipine, or verapamil are initiated or discontinued. The dosage of sirolimus or tacrolimus may need to be adjusted or the calcium channel blocker may need to be discontinued. Patients receiving concurrent sirolimus and verapamil should be observed for increased verapamil effects. The US manufacturer of sirolimus protein-bound injection (Fyarro) states a dose reduction to 56 mg/m2 is recommended when used concurrently with moderate or weak CYP3A4 inhibitors. Concurrent use with strong CYP3A4 inhibitors should be avoided.(4) Sirolimus is the active metabolite of temsirolimus,(3) therefore, temsirolimus is expected to act in the same manner as sirolimus. DISCUSSION: In an open, randomized, cross-over trial in 18 healthy subjects, concurrent single doses of diltiazem (120 mg) and sirolimus (10 mg) increased sirolimus area-under-curve (AUC) and maximum concentration (Cmax) by 60% and by 43%, respectively. Sirolimus apparent oral clearance and volume of distribution decreased by 38% and 45%, respectively. There were no effects on diltiazem pharmacokinetics or pharmacodynamics.(1,2) In a study in 24 healthy subjects, concurrent single doses of nifedipine (60 mg) and sirolimus (10 mg) had no effect on sirolimus levels.(1) Nicardipine may increase sirolimus levels.(1) In a study in 26 healthy subjects, concurrent sirolimus (2 mg daily) with verapamil (180 mg twice daily) increased sirolimus AUC and Cmax by 2.2-fold and 2.3-fold, respectively. The AUC and Cmax of the active S-enantiomer of verapamil each increased by 1.5-fold. Verapamil time to Cmax (Tmax) was increased by 1.2 hours.(1) Sirolimus is the active metabolite of temsirolimus,(2) therefore, temsirolimus is expected to act in the same manner as sirolimus. In a study in 25 healthy subjects, concurrent sirolimus with verapamil increased sirolimus Cmax and AUC 130% and 120%, respectively.(5) |
SIROLIMUS, TEMSIROLIMUS, TORISEL |
| Tamoxifen/Selected Weak CYP2D6 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of CYP2D6 may inhibit the conversion of tamoxifen to endoxifen (an active metabolite of tamoxifen).(1-2) The role of endoxifen in tamoxifen's efficacy has been debated and may involve a minimum concentration level.(3-5) CLINICAL EFFECTS: Concurrent use of inhibitors of CYP2D6 may decrease the effectiveness of tamoxifen in preventing breast cancer recurrence. PREDISPOSING FACTORS: Concurrent use of weak CYP2D6 inhibitors in patients who are CYP2D6 intermediate metabolizers should be avoided. Patients who are CYP2D6 poor metabolizers lack CYP2D6 function and are not affected by CYP2D6 inhibition. PATIENT MANAGEMENT: Although data on this interaction are conflicting, it may be prudent to use alternatives to CYP2D6 inhibitors when possible in patients taking tamoxifen. The US manufacturer of tamoxifen states that the impact on the efficacy of tamoxifen by strong CYP2D6 inhibitors is uncertain and makes no recommendation regarding coadministration with inhibitors of CYP2D6.(12) The manufacturer of paroxetine (a strong CYP2D6 inhibitor) states that alternative agents with little or no CYP2D6 inhibition should be considered.(13) The National Comprehensive Cancer Network's breast cancer guidelines advises caution when coadministering strong CYP2D6 inhibitors with tamoxifen.(14) If concurrent therapy is warranted, the risks versus benefits should be discussed with the patient. DISCUSSION: Some studies have suggested that administration of fluoxetine, paroxetine, and quinidine with tamoxifen or a CYP2D6 poor metabolizer phenotype may result in a decrease in the formation of endoxifen (an active metabolite of tamoxifen) and a shorter time to breast cancer recurrence.(1-2,9) A retrospective study of 630 breast cancer patients found an increasing risk of breast cancer mortality with increasing durations of coadministration of tamoxifen and paroxetine. In the adjusted analysis, absolute increases of 25%, 50%, and 75% in the proportion of time of overlapping use of tamoxifen with paroxetine was associated with 24%, 54%, and 91% increase in the risk of death from breast cancer, respectively.(16) The CYP2D6 genotype of the patient may have a role in the effects of this interaction. Patients with wild-type CYP2D6 genotype may be affected to a greater extent by this interaction. Patients with a variant CYP2D6 genotype may have lower baseline levels of endoxifen and may be affected to a lesser extent by this interaction.(6-10) In a retrospective review, 1,325 patients treated with tamoxifen for breast cancer were classified as being poor 2D6 metabolizers (lacking functional CYP2D6 enzymes), intermediate metabolizers (heterozygous alleles), or extensive metabolizers (possessing 2 functional alleles). After a mean follow-up period of 6.3 years, the recurrence rates were 14.9%, 20.9%, and 29.0%, in extensive metabolizers, intermediate metabolizers, and poor metabolizers, respectively.(11) In October of 2006, the Advisory Committee Pharmaceutical Science, Clinical Pharmacology Subcommittee of the US Food and Drug Administration recommended that the US tamoxifen labeling be updated to include information about the increased risk of breast cancer recurrence in poor CYP2D6 metabolizers (either by genotype or drug interaction).(17-18) The labeling changes were never made due to ongoing uncertainty about the effects of CYP2D6 genotypes on tamoxifen efficacy. In contrast to the above information, two studies have shown no relationship between CYP2D6 genotype and breast cancer outcome.(19-21) As well, a number of studies found no association between use of CYP2D6 inhibitors and/or antidepressants in patients on tamoxifen and breast cancer recurrence,(22-26) though the studies were limited by problematic selection of CYP2D6 inhibitors and short follow-up. Weak inhibitors of CYP2D6 include: alogliptin, artesunate, celecoxib, cimetidine, clobazam, cobicistat, delavirdine, diltiazem, dimenhydrinate, diphenhydramine, dronabinol, dupilumab, echinacea, enasidenib, fedratinib, felodipine, fluvoxamine, gefitinib, hydralazine, imatinib, labetalol, lorcaserin, nicardipine, osilodrostat, ranitidine, ritonavir, sertraline, verapamil and viloxazine.(27) |
SOLTAMOX, TAMOXIFEN CITRATE |
| Selected Calcium Channel Blockers/Selected Strong CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong CYP3A4 inhibitors may inhibit the first-pass and elimination metabolism of calcium channel blockers by CYP3A4. CLINICAL EFFECTS: The concurrent use of strong CYP3A4 inhibitors with calcium channel blockers metabolized by CYP3A4 may result in elevated levels of the calcium channel blocker and risk of adverse effects, including hypotension and bradycardia. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of strong CYP3A4 inhibitors with calcium channel blockers should be approached with caution. When these agents are used concurrently, the dose of the calcium channel blocker may need to be adjusted or an alternative agent considered. Monitor patients for increased calcium channel blocker effects. If the strong CYP3A4 inhibitor is discontinued, the dose of the calcium channel blocker may need to be increased and patients should be observed for decreased effects. DISCUSSION: A double-blind, randomized, two-phase crossover study in nine subjects examined the effects of itraconazole on felodipine. The half-life of felodipine increased by 71% during concurrent itraconazole. In seven of the nine subjects, the maximum concentration (Cmax) of felodipine when administered with placebo was lower than the 32-hour concentration of felodipine when administered with itraconazole. Concurrent use also resulted in significantly greater effects on both blood pressure and heart rate.(10,11) A randomized cross-over trial in seven subjects examined the effects of ketoconazole (200 mg daily for 4 days) on nisoldipine (5 mg daily). The concurrent use of ketoconazole increased the nisoldipine area-under-curve (AUC) and Cmax by 24-fold and 11-fold, respectively. Increases in the M9 nisoldipine metabolite were similar.(7) PKPB modeling of nifedipine and ritonavir noted a decreased systolic blood pressure > 40 mmHg.(8) There are several case reports of patients developing increased levels of calcium channel blockers and adverse effects with concurrent strong CYP3A4 inhibitors.(9-16) Strong CYP3A4 inhibitors include: adagrasib, ceritinib, cobicistat, grapefruit, idelalisib, indinavir, itraconazole, ketoconazole, levoketoconazole, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, posaconazole, ribociclib, saquinavir, tipranavir, troleandomycin, tucatinib, and voriconazole.(17,18) |
APTIVUS, EVOTAZ, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, POSACONAZOLE, PREZCOBIX, RECORLEV, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VORICONAZOLE, ZYDELIG, ZYKADIA |
| Tizanidine/Selected Antihypertensives SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4) |
TIZANIDINE HCL, ZANAFLEX |
| Lacosamide/Beta-Blockers; Calcium Channel Blockers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Lacosamide may enhance the slow inactivation of voltage-gated sodium channels and may cause dose-dependent bradycardia, prolongation of the PR interval, atrioventricular (AV) block, or ventricular tachyarrhythmia.(1) CLINICAL EFFECTS: Concurrent use of lacosamide and agents that affect cardiac conduction (beta-blockers, calcium channel blockers) may increase the risk of bradycardia, prolongation of the PR interval, atrioventricular (AV) block, or ventricular tachyarrhythmia.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Lacosamide should be used with caution in patients on concomitant medications that affect cardiac conduction, including beta-blockers and calcium channel blockers.(1) If concurrent use is needed, obtain an ECG before lacosamide therapy and after lacosamide dose is titrated to steady-state.(1) Patients should be monitored closely when lacosamide is given intravenously.(1) DISCUSSION: In a clinical trial in patients with partial-onset seizures, asymptomatic first-degree atrioventricular (AV) block occurred in 4/944 (0.4%) of patient who received lacosamide compared to 0/364 (0%) with placebo.(1) In a clinical trial in patients with diabetic neuropathy, asymptomatic first-degree AV block occurred in 5/1023 (0.5%) of patients who received lacosamide compared to 0/291 (0%) with placebo.(1) Second-degree and complete AV block have been reported in patients with seizures.(1) One case of profound bradycardia was observed in a patient during a 15-minute infusion of 150 mg of lacosamide.(1) Two postmarketing reports of third-degree AV block in patients with significant cardiac history and also receiving metoprolol and amlodipine during infusion of lacosamide injection at doses higher than recommended have been reported.(1) A case report of an 88 year old female taking bisoprolol documented complete AV block after initiation of lacosamide. The patient required pacemaker implementation.(2) |
LACOSAMIDE, MOTPOLY XR, VIMPAT |
| Apomorphine/Selected Antihypertensives and Vasodilators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1) PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1) PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1) |
APOKYN, APOMORPHINE HCL, ONAPGO |
| Selected Calcium Channel Blockers/Nirmatrelvir-Ritonavir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Nirmatrelvir-ritonavir may inhibit the metabolism of calcium channel blockers by CYP3A4.(1,2) CLINICAL EFFECTS: Concurrent use of nirmatrelvir-ritonavir may result in elevated levels of and toxicity from calcium channel blockers. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of nirmatrelvir-ritonavir and selected calcium channel blockers should be approached with caution. Monitor patients receiving concurrent therapy with nirmatrelvir-ritonavir and either amlodipine, diltiazem, felodipine, nicardipine, nifedipine, or verapamil for increased calcium channel blocker effects. The dosage of the calcium channel blocker may need to be adjusted.(1,2) The Journal of American College of Cardiology recommends a 50% reduction in the dose amlodipine for 8 days with the initiation of nirmatrelvir-ritonavir. Close monitoring of blood pressure and dose reduction or temporary discontinuation of calcium channel blockers may be needed. Resume calcium channel blockers 3 days after the last dose of nirmatrelvir-ritonavir.(3) DISCUSSION: Nirmatrelvir-ritonavir is a strong CYP3A4 inhibitor and may increase the levels of calcium channel blockers that are CYP3A4 substrates.(1,2) In a case report of a 80-year old female on verapamil, on day 2 of concurrent nirmatrelvir-ritonavir the patient presented to the hospital with symptomatic bradycardia (heart rate of 28 beats per minute and blood pressure of 58/35 mmHg) requiring hospitalization, medical management, and a temporary transvenous pacer.(4) |
PAXLOVID |
The following contraindication information is available for CARDENE I.V. (nicardipine hcl):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Severe aortic valve stenosis |
There are 5 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic heart failure |
| Chronic idiopathic constipation |
| Disease of liver |
| Hypotension |
| Intracerebral hemorrhage |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Angina |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
The following adverse reaction information is available for CARDENE I.V. (nicardipine hcl):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 12 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Tachycardia |
None. |
| Rare/Very Rare |
|---|
|
Abnormal ECG Acute myocardial infarction Angina Atrioventricular block Deep venous thrombosis Hypophosphatemia Hypoxia Peripheral edema Severe hypotension Sinus node dysfunction Thrombocytopenic disorder |
There are 14 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Headache disorder Hypotension Nausea Vomiting |
None. |
| Rare/Very Rare |
|---|
|
Acute cognitive impairment Conjunctivitis Dyspepsia Fever Hypertonia Increased urinary frequency Injection site sequelae Neck pain Thrombophlebitis Tinnitus |
The following precautions are available for CARDENE I.V. (nicardipine hcl):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Nicardipine hydrochloride has been shown to be embryocidal in pregnant Japanese white rabbits when given at an oral daily dose of 150 mg/kg (a dosage associated with marked body weight gain suppression in the treated doe) during organogenesis but not at a daily dose of 50 mg/kg (25 times the maximum recommended human dosage). There was no evidence of embryotoxicity or teratogenicity when nicardipine hydrochloride was administered IV at dosages up to 5 mg/kg daily in pregnant rats or up to 0.5 mg/kg daily in pregnant rabbits.
Embryotoxicity was observed at IV dosages of 10 mg/kg daily in rats and 1 mg/kg daily in rabbits, but there was no evidence of teratogenicity at these dosages. No adverse effects on the fetus were observed when New Zealand albino rabbits received nicardipine hydrochloride dosages up to 100 mg/kg daily (a dose associated with mortality in the treated doe) during organogenesis. Pregnant rats receiving oral nicardipine hydrochloride at dosages up to 100 mg/kg daily (50 times the maximum recommended human dosage) did not exhibit evidence of embryolethality or teratogenicity but did exhibit evidence of dystocia, reduced birthweights, reduced neonatal survival, and reduced neonatal weight gain.
There are no adequate and controlled studies to date using nicardipine in pregnant women. Oral and IV nicardipine have been used effectively for the management of hypertension and preeclampsia during the third trimester in a limited number of women and were well tolerated and apparently did not affect the fetus adversely. Nicardipine crosses the placenta, but fetal plasma concentrations are only approximately 10% of concurrent maternal plasma concentrations. Nicardipine should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
Embryotoxicity was observed at IV dosages of 10 mg/kg daily in rats and 1 mg/kg daily in rabbits, but there was no evidence of teratogenicity at these dosages. No adverse effects on the fetus were observed when New Zealand albino rabbits received nicardipine hydrochloride dosages up to 100 mg/kg daily (a dose associated with mortality in the treated doe) during organogenesis. Pregnant rats receiving oral nicardipine hydrochloride at dosages up to 100 mg/kg daily (50 times the maximum recommended human dosage) did not exhibit evidence of embryolethality or teratogenicity but did exhibit evidence of dystocia, reduced birthweights, reduced neonatal survival, and reduced neonatal weight gain.
There are no adequate and controlled studies to date using nicardipine in pregnant women. Oral and IV nicardipine have been used effectively for the management of hypertension and preeclampsia during the third trimester in a limited number of women and were well tolerated and apparently did not affect the fetus adversely. Nicardipine crosses the placenta, but fetal plasma concentrations are only approximately 10% of concurrent maternal plasma concentrations. Nicardipine should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
Nicardipine is distributed into milk in high concentrations in rats. Because of the potential for serious adverse reactions to nicardipine in nursing infants, it is recommended that women who breastfeed not be given the drug.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for CARDENE I.V. (nicardipine hcl):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for CARDENE I.V. (nicardipine hcl)'s list of indications:
| Hypertension | |
| I10 | Essential (primary) hypertension |
| I11 | Hypertensive heart disease |
| I11.0 | Hypertensive heart disease with heart failure |
| I11.9 | Hypertensive heart disease without heart failure |
| I12 | Hypertensive chronic kidney disease |
| I12.0 | Hypertensive chronic kidney disease with stage 5 chronic kidney disease or end stage renal disease |
| I12.9 | Hypertensive chronic kidney disease with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease |
| I13 | Hypertensive heart and chronic kidney disease |
| I13.0 | Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease |
| I13.1 | Hypertensive heart and chronic kidney disease without heart failure |
| I13.10 | Hypertensive heart and chronic kidney disease without heart failure, with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease |
| I13.11 | Hypertensive heart and chronic kidney disease without heart failure, with stage 5 chronic kidney disease, or end stage renal disease |
| I13.2 | Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end stage renal disease |
| I15.1 | Hypertension secondary to other renal disorders |
Formulary Reference Tool